Intranasal monkeypox marmoset model: Prophylactic antibody treatment provides benefit against severe monkeypox virus...

Area of Science:

• Virology
• Pathology
• Immunology

Background:

• Human monkeypox outbreaks and the potential reintroduction of smallpox necessitate robust animal models and effective countermeasures.
• Existing models may not fully replicate natural exposure routes or disease progression.

Purpose of the Study:

• To establish a marmoset model for monkeypox and smallpox disease using a relevant poxvirus and natural exposure route.
• To evaluate the efficacy of monoclonal antibodies as a countermeasure in this model.
• To investigate potential gender-based differences in disease manifestation.

Main Methods:

• Exposure of marmosets to 1000 plaque-forming units (PFU) of Monkeypox virus via a natural route.
• Monitoring disease progression, including incubation period, rash onset, mortality, viremia, and oral shedding.
• Prophylactic administration of two monoclonal antibodies (c7D11 and c8A) to assess therapeutic efficacy.

Main Results:

• Monkeypox virus infection recapitulated smallpox disease with a ~13-day incubation period, rash, and death between days 15-17.
• Viremia and oral shedding were observed, with lesion counts ranging up to 299.
• Prophylactic antibody treatment protected 2 out of 3 marmosets; the third succumbed to disease.
• Female marmosets exhibited more lesions and lower viral burden compared to males.

Conclusions:

• The marmoset model effectively replicates key features of monkeypox and smallpox, serving as a valuable platform for studying poxvirus diseases.
• Monoclonal antibodies demonstrate potential as effective countermeasures against poxvirus infections.
• Observed gender-based differences warrant further investigation into sex-specific responses to poxvirus infection.